A Phase 1, Non- Randomized, Open Label, Sequential Group, Multicenter Study To Evaluate The Antiviral Activity Of Multiple Doses Of A Small Molecule Direct Antiviral Agent In Chronically Infected Hepatitis C Subjects.
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Pfizer
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Full Analysis Set
Study Overview
Brief Summary
Phase 1 study in HVC (Hepatitis C Virus) infected subjects to determine pharmacokinetics, safety and efficacy in subjects with no or inadequate response to prior treatment.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •HCV Positive With HCV RNA>100,000 iu/ml Genotype 1; COHORT A- non responders or partial
Exclusion Criteria
- •HIV HBV co-infection Decompensated liver disease Liver disease due to causes other than HCV, AFP>200ng/ml
Arms & Interventions
Cohort B
Intervention: Small Molecule Agent (PF-868554) (Drug)
Cohort A
Dose study drug in subjects who have previously failed to respond to interferon based therapies
Intervention: Small Molecule Agent (PF-868554) (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Full Analysis Set
Time Frame: Baseline, Day 11
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (lower limit of quantification \[LLOQ\] = 12 international unit per milliliter \[IU/mL\]). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 11 for Cohort A).
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 11 (Cohort A): Modified Analysis Set
Time Frame: Baseline, Day 11
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 11 for Cohort A).
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Full Analysis Set
Time Frame: Baseline, Day 4
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as an average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 4 for Cohort B).
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 4 (Cohort B): Modified Analysis Set
Time Frame: Baseline, Day 4
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Baseline value calculated as the average of screening, Day 0 and Day 1 (0 hour) measurements. Change from baseline in plasma log10 HCV RNA was calculated for all participants after the last day of dosing (Day 4 for Cohort B).
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Full Analysis Set
Time Frame: Baseline, Nadir (lowest HCV RNA level), assessed up to Day 11 for Cohort A and Day 4 for Cohort B
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Change from baseline in plasma Log10 HCV RNA at nadir signified the maximum change observed during the study.
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Nadir: Modified Analysis Set
Time Frame: Baseline, Nadir (lowest HCV RNA level), assessed up to Day 11 for Cohort A and Day 4 for Cohort B
Plasma HCV RNA levels were quantified using the Abbott RealTime HCV assay (LLOQ = 12 IU/mL). Change from baseline in plasma Log10 HCV RNA at nadir signified the maximum change observed during the study.
Secondary Outcomes
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)(Predose, 0.5, 1, 2, 6, 8, 12 hours (hrs) postdose on Day 1 for Cohort A and B, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12 hrs post-evening dose on Day 3 for Cohort B, predose, 0.5, 1, 2, 4, 8, 12 hrs postdose on Day 10 for Cohort A)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)(Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A)
- Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)](Pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A)
- Plasma Concentration at The End of Dosing Interval (Ctau)(Predose, 0.5, 1, 2, 6, 8, 12 hours (hrs) postdose on Day 1 for Cohort A and B, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12 hrs post-evening dose on Day 3 for Cohort B, predose, 0.5, 1, 2, 4, 8, 12 hrs postdose on Day 10 for Cohort A)
- Maximum Observed Plasma Concentration (Cmax)(Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(Predose, 0.5, 1, 2, 6, 8, 12, 14 hrs postdose on Day 1 for Cohort A, B, pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A)
- Plasma Decay Half-Life (t1/2)(Pre-morning dose, pre-evening dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 hrs post-evening dose on Day 3 for Cohort B, predose,0.5, 1, 2, 4, 8, 12, 24, 48 hrs postdose on Day 10 for Cohort A)